In vivo efficacy of human recombinant factor IX produced by the human hepatoma cell line HuH-7.

INTRODUCTION: Post-translational modifications of the CHO-cell-derived-recombinant human factor IX (FIX) currently used for the treatment of hemophilia B (HB) are different from plasma derived FIX. Our previous studies described a rFIX (HIX) having better profile of post-translational modifications than rFIX produced by CHO cells. The aim of the study consisted to verify the improved post-translational modifications effect of HIX on in vivo recovery. MATERIALS AND METHODS: HIX has been produced in a bioreactor and then purified from supernatants. In vitro activation and activity were evaluated measured by thrombin generation tests (TGT) and compared to commercial molecules, Benefix(®) , Mononine(®) . The three molecules were then administrated (i.v.) to FIX-knockout mice and two minutes after injection, blood samples were collected and subjected to human FIX-specific-ELISA and TGT. RESULTS: The clotting function of HIX, activation courses of HIX by FXIa and FVIIa-TF complex appear normal as did activation of Benefix(®) , Mononine(®) and TG constants of each FIX were equivalent. After injection to HB mice, circulating HIX did not present any significant difference in term of antigen value with Benefix(®) . Intriguingly, TGT were clearly exhibiting a better velocity for HIX than Benefix(®) and Mononine(®) . These data suggested that HIX may improve in vivo coagulant efficacy in comparison with the two commercial FIX injected at the same dose. CONCLUSION: The study shows that HuH-7-derived-rFIX has better in vivo haemostatic activity in hemophilia B mice compared to the reference rFIX molecule despite similar in vivo recovery rates, suggesting that HuH-7 cells could represent an effective cellular system for production of rFIX.

Earlier onset and poor prognosis of lung cancer in imprisoned patients.

INTRODUCTION: Prison inmates are known to be more exposed to various lung cancer risk factors, and some studies have shown that lung cancer is the most common cancer in prisoners. However, no study has particularly focused on lung cancer features in this population. METHOD: Charts of patients with lung cancer hospitalized in one of the French secured hospital units between 1997 and 2012 were reviewed. Data from this cohort were then compared to those of two large observational studies conducted in 2000 and 2010 (KBP studies). RESULTS: Thirty-two cases were included. All were men. The mean age was 52.2 ± 11.5 years, which was significantly lower than in the KBP-2000 (64.4 years) and KBP-2010 (65.5 years; both p < 0.0001) studies. The percentage of current smokers was much higher in prisoners (87.1 vs. 52.2 and 49.2%, respectively; both p < 0.001). Ninety percent of prisoners presented with at least one comorbidity. Lung cancer clinical presentation did not differ between prisoners and the reference populations. The median overall survival was 5.8 months (range 0-15.1) for all stages and 4.7 months (range 2.8-6.6) for stage IIIB/IV. CONCLUSION: Although our study suffers from limitations, prisoners seem to develop lung cancer at a younger age and their prognosis is poor.